Purified water equipment for GMP certification
Release date: November 27, 2019 11:33:48
Requirements of GMP for purified water system
Pharmaceutical production water should be suitable for its use, and at least drinking water should be used as pharmaceutical water. All kinds of pharmaceutical water in the Pharmacopoeia of the people's Republic of China should meet the requirements of pharmaceutical production. Drinking water should meet the relevant national quality standards, purified water and water for injection should meet the quality standards of Pharmacopoeia of the people's Republic of China.
The design, installation and maintenance of the water treatment equipment and its delivery system shall ensure that the pharmaceutical water meets the set quality standards. The operation of water treatment equipment shall not exceed its design capacity.
The materials used in purified water and injection water storage tank and transmission pipeline should be non-toxic and corrosion-resistant; the vent of storage tank should be installed with hydrophobic sterilization filter without fiber shedding; the design and installation of pipeline should avoid dead angle and blind pipe. Water quality and water quality should be monitored regularly.
The preparation, storage and distribution of purified water and water for injection should be able to prevent the growth of microorganisms. For example, the water for injection can be recycled at a temperature above 70 ℃.
The purified water, water for injection pipelines, storage tanks and other necessary auxiliary pipelines (such as pipelines for cleaning and disinfection, and temporary connecting pipelines for production) shall be disinfected regularly according to the operation procedures, and relevant records shall be kept. The operating procedures should also specify the warning limit, correction limit and measures to be taken.
Requirements for purified water equipment for GMP certification
1. The structure design should be simple, reliable and easy to disassemble and assemble.
2. In order to facilitate the disassembly, replacement and cleaning of parts, the actuator design should adopt standardized, universal and systematic parts as far as possible.
3. The surface of internal and external walls of the equipment shall be smooth, flat, free of dead angle, easy to clean and sterilize. The surface of parts shall be treated with chromium plating to prevent corrosion and rust. Avoid using paint on the outside of the equipment to prevent spalling.
4. Low carbon stainless steel or other verified materials that do not pollute the water quality should be used in the purified water preparation equipment. The equipment for preparing purified water should be cleaned regularly and the cleaning effect should be verified.
5. The materials in contact with water for injection must be high-quality low-carbon stainless steel (such as 316L stainless steel) or other verified materials that do not pollute the water quality. The equipment for preparing water for injection should be cleaned regularly and the cleaning effect should be verified.
6. The storage period of purified water should not be longer than 24 hours, and the storage tank should be made of stainless steel or other materials that have been verified to be non-toxic, corrosion-resistant and do not exude polluting ions. Hydrophobic filter with no fiber shedding should be installed to protect the vent. The inner wall of the storage tank shall be smooth, and there shall be no dead angle and sand hole in the connecting pipe and welding seam. The sensor which will not form stagnant water pollution should be used to display the parameters such as liquid level, temperature and pressure. The storage tank should be cleaned, disinfected and sterilized regularly, and the cleaning and sterilization effect should be verified.
7. Pharmaceutical water delivery
1) the purified water and pharmaceutical water should be transported by stainless steel pump which is easy to disassemble, clean and disinfect. When the purified water and water for injection need to be delivered by compressed air or nitrogen pressure, the compressed air and nitrogen must be purified.
2) the purified water should be transported by circulating pipeline. The pipeline design should be simple and avoid blind pipe and dead angle. The pipeline shall be stainless steel pipe or other proven non-toxic, corrosion-resistant and non exudating pollution ions. The valve should be sanitary valve without dead angle, and the flow direction of purified water should be indicated.
3) the pipelines and pumps conveying purified water and water for injection should be cleaned, disinfected and sterilized regularly, and can be put into use only after passing the verification.
8. The design of pressure vessels shall be undertaken by licensed units and qualified personnel, and shall be handled in accordance with the relevant provisions of the national standards of the people's Republic of China "steel pressure vessels" (gb150-80) and "safety technology supervision regulations for pressure vessels".
Our company develops and produces water treatment system according to GMP requirements
The production of pharmaceutical purified water usually has the following two processes, and the process route can also be determined according to customer requirements
1) raw water, raw water tank, raw water pump, multi-media filter, activated carbon filter, softener, primary precision filter, primary reverse osmosis, secondary reverse osmosis, ozone generator, purified water tank, ultraviolet sterilizer, pure water pump and water consumption point.
2) raw water, raw water tank, raw water pump, multi-media filter, activated carbon filter, softener, primary precision filter, primary reverse osmosis, mixed ion exchanger, ozone generator, pure water tank, ultraviolet sterilizer, pure water pump and water consumption point.
Brief introduction to functions of each unit of purified water equipment for GMP certification
1. Automatic backwashing multi-media filter
Most of the multi-media filter tanks are filled with quartz sand, anthracite and manganese sand. Its main function is to reduce the turbidity of water, and can remove a large number of bacteria, viruses, organic matter and so on. So as to create favorable conditions for the subsequent disinfection process. Manganese sand has remarkable removal effect on iron and manganese.
2. Automatic backwashing activated carbon filter tank
Coconut shell activated carbon
Activated carbon has a large number of micropores and large specific surface area, which has a strong physical adsorption capacity. It can effectively adsorb impurities in water, especially organic matter and microorganism. Some metal ions in water can be removed by oxygen-containing catalytic oxidation and chemisorption formed on the surface of activated carbon. Activated carbon has a strong adsorption effect on residual chlorine in water to protect the downstream stainless steel equipment and pipe surface and meet the water inflow requirements of the subsequent water treatment unit.
3. Automatic recoil and regeneration softening tank
The softening tank is filled with sodium type cation exchange resin. Through the ion exchange reaction of resin, the hardness of water can be reduced, and the combination of calcium and magnesium ions with carbonate and sulfate ions can be prevented from scaling in the subsequent water treatment equipment or pipeline.
Precision filter, 4
Precision filter is also known as security filter, the filtering accuracy is generally 5 μ M. Its function is to intercept all materials with particle size greater than 5 μ m to meet the requirements of reverse osmosis.
5. Reverse osmosis
The key to the application of reverse osmosis technology lies in the performance of reverse osmosis membrane which plays the role of desalting. Reverse osmosis (RO) membrane is a kind of semi permeable membrane which only allows water molecules to pass through but not solute. In addition to the principle of reverse osmosis and reverse osmosis, reverse osmosis technology also uses membrane selective adsorption and screening mechanism for organic matter. Most of the pore sizes of reverse osmosis membranes are less than or equal to 10 × 10-10 m, and the separation objects are organic compounds in the ionic range and molecular weight of several hundred or so. It can filter out all kinds of bacteria, such as Pseudomonas aeruginosa (3000 × 10-10m), virus (800 × 10-10m), meningoinflammatory virus (200 × 10-10m), and pyrogen (10-500 × 10-10m). This is a question about how much water is used to make medicine.
Because of its simple operation process and high desalination efficiency, reverse osmosis has high pyrogen removal capacity and economic efficiency when used in pharmaceutical process water, so it has become the preferred water treatment unit in pharmaceutical water process. Reverse osmosis technology is not only used in the preparation process of purified water, but also can be used to produce water with injection quality. Since the 19th edition of the United States Pharmacopoeia, this method has been included as one of the statutory methods for the preparation of water for injection.
6. Electrical deionization (EDI)
Electrical ion exchange system (EDI) is also an ion exchange system. This ion exchange system uses a mixed resin bed, a selective permeable membrane and a charger to ensure continuous water treatment and continuous regeneration of resin. The treatment process is that the raw water first enters the resin section, and when the water passes through the resin, the metal charge ions are removed and the product water is formed. The potential of the cation trapped in the resin can be seen as the potential of the resin to be desorbed through the membrane. At the same time, in the resin section, the potential energy of the potential electrolyzes the water into hydrogen ions and hydroxyl ions, so that the resin can be continuously regenerated without adding regenerant.
7. Sterilization system
A. oxygen and ultraviolet are combined orderly for disinfection / sterilization. Ozone is a kind of strong oxidant, its oxidation capacity in natural elements only this and fluorine, ranked second. Ozone can oxidize and decompose glucose oxidase necessary for glucose oxidation in bacteria,
It can also directly interact with bacteria and viruses, destroy cells and ribonucleic acids, decompose DNA, RNA, protein, lipids and polysaccharides and other macromolecular polymers, thus destroying the metabolic growth and reproduction process of bacteria. In water treatment
Decolorization, sterilization, removal of phenol, cyanogen, iron and manganese, and reduction of COD and BOD have significant effects. UV light can reduce the formation rate of new colonies in the pretreatment system of water system, and the 254 nm ultraviolet lamp after ozone can be used for disinfection and ozone removal simultaneously.
B. circulating reflux to prevent bacterial growth. In the purified water system, the pretreatment system, the water preparation system and the water system are respectively provided with circulating water. When the water is not used on holidays or at night, when the purified water tank is full, and when the effluent conductivity exceeds the standard, each system is provided with circulating water
If necessary, ultraviolet or ozone / ultraviolet sterilization should be supplemented to prevent bacterial growth.
The effluent quality of purified water equipment for GMP certification meets GMP requirements
Our technical personnel will design appropriate water treatment process according to the water quality of users to meet the effluent requirements.
For the water whose quality exceeds the standard, the equipment will discharge automatically to ensure the quality of effluent. If the user needs, our company can provide the relevant information of the water making equipment to cooperate with the user to pass the GMP.
The sterilization system of purified water equipment for GMP certification meets GMP design requirements
In order to effectively control sanitary pollution and control the level of bacterial endotoxin at the same time, there are two characteristics in the design and construction of pharmaceutical system: one is the increasing use of disinfection / sterilization facilities in the system; the other is the evolution from the traditional one-way flow type to the circulation reflux type. High temperature disinfection is not suitable for ion exchange resin, reverse osmosis and electric deionization in purified water system, otherwise it will be aged, broken or damaged. Ozone / UV disinfection and circulation reflux method can be used. These cutting-edge technologies have been fully reflected in our products.
In order to prevent the growth of microorganisms caused by the retention of liquid or material in the equipment system, the inner wall of the equipment is required to be smooth without dead angle, and the pipeline design shall be free of redundant branch pipes, pipe fittings, valves and blind pipes. The pipeline design should follow the water supply pipeline as far as possible, and should be arranged vertically near the
The principle of horizontal introduction near water equipment. Try not to arrange the horizontal pipe above the equipment to prevent the static retention of water on the horizontal pipe.
The length of the branch pipe introduced from the vertical pipe should be short, generally no more than 6 times of the diameter of the branch pipe. The bending radius of the pipeline should be as large as possible. If the bending radius of the pipe is small, it is easy to form liquid accumulation. The valves in the pipeline are mostly cocks, ball valves, diaphragm valves, sanitary butterfly valves and sanitary stop valves, which are not easy to form liquid accumulation, so as to avoid the use of ordinary stop valves and gate valves. Screw connection shall be avoided to the greatest extent in pipeline connection, and butt flange and looper flange which are not easy to form liquid accumulation shall be adopted.
Purified water equipment for GMP certification meets GMP material requirements
The materials selected for the purified water equipment and pipelines for GMP certification are determined according to the physical and chemical properties and service conditions of the materials loaded, stored and transported, taking into account the process requirements, not absorbing and polluting the medium, and convenient construction and maintenance, so as to reduce the pollution of the materials to drugs and drugs.
UPVC is selected as the pipe material for general water outlet requirements;
316L should be selected for the equipment and pipe material with certain water outlet requirements;
PVDF is selected as piping material for special effluent requirements
High quality stainless steel pipe